title: Effects of combination treatment of bortezomib and dexamethasone in SCCHN cell lines depend on tumor cell specificity.
abstract: Bortezomib has recently become the new treatment standard for relapsed or refractory multiple myeloma. We previously demonstrated that bortezomib also had a significant growth-inhibiting and apoptotic effect on squamous cell carcinoma of the head and neck (SCCHN) cells in vitro. Preclinical evidence has provided a rationale for combining bortezomib with dexamethasone in multiple myeloma, suggesting that the therapeutic effects of the two agents might be additive. These findings are in contrast with the results achieved in solid tumor models where the addition of dexamethasone reduced the efficacy of other antineoplastic drugs. In the present study, we investigated the effect of dexamethasone in combination with bortezomib in SCCHN cell lines for the first time. The antiproliferative effect of bortezomib alone or in combination with increasing concentrations of dexamethasone was investigated in four SCCHN cell lines. Cell growth inhibition and viability were measured quantitatively using WST and LDH assays. Bortezomib alone inhibited the growth of all four SCCHN cell lines significantly (p<0.047). The addition of dexamethasone leads to a clear tumor cell decline and showed a trend in enhancing the growth-inhibitory effect of bortezomib although the difference failed to reach statistical significance (p>0.05). Our first results show that dexamethasone increased the cytotoxic activity of bortezomib in most SCCHN cell lines investigated. These findings might be dependent on molecular factors such as the degree of tumor cell differentiation and proliferation rate. Therefore, further studies will be required to elucidate these molecular factors to substantiate our findings from a cancer biological point of view.
authors.affiliation: ENT Department, Goethe University Medical School, Frankfurt am Main, Germany. jens.wagenblast@kgu.de
authors.forename: Jens
authors.initials: J
authors.lastname: Wagenblast
authors.forename: Mehran
authors.initials: M
authors.lastname: Baghi
authors.forename: Christoph
authors.initials: C
authors.lastname: Arnoldner
authors.forename: Sotirios
authors.initials: S
authors.lastname: Bisdas
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Gstöttner
authors.forename: Angelika
authors.initials: A
authors.lastname: May
authors.forename: Rainald
authors.initials: R
authors.lastname: Knecht
authors.forename: Markus
authors.initials: M
authors.lastname: Hambek
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D001897:Boronic Acids / Q000008:administration & dosage; D000069286:Bortezomib; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D003907:Dexamethasone / Q000008:administration & dosage; D004354:Drug Screening Assays, Antitumor; D006258:Head and Neck Neoplasms / Q000188:drug therapy*; D006801:Humans; D011719:Pyrazines / Q000008:administration & dosage
chemical_list: D001897:Boronic Acids; D011719:Pyrazines; D000069286:Bortezomib; D003907:Dexamethasone